HEPATIC EXPRESSION OF CYCLOOXYGENASE-2 IN NON-ALCOHOLIC FATTY LIVER DISEASE

Hsp60 quantification in human gastric mucosa shows differences between pathologies with various degrees of proliferation and malignancy grade

Background: Stomach diseases are an important sector of gastroenterology, including proliferative benign

Metastatic seeding of colon adenocarcinoma manifesting as synchronous breast and chest wall localization: report of a case.

Colon carcinoma rarely metastasizes to the breast and it is usually associated with a poor prognosis. Even rarer is metastatic seeding of colon cancer cells in an intramammary location after surgery. Including a primary breast malignancy in the differential diagnosis of such cases is mandatory. We report a rare case of double seeding implantation of colon adenocarcinoma inside the breast parenchyma and intercostal muscles 6 years after resection of a pulmonary metastasis from colon adenocarcinoma. The metastasis was revealed by the presence of bone metaplasia in the intercostal muscles. We discuss how negative immunostaining for estrogen receptors, progesterone receptors, and HER-2, along w…

Associations between Notch-2, Akt-1 and HER2/neu expression in invasive human breast cancer: a tissue microarray immunophenotypic analysis on 98 patients.

<i>Objective:</i> We aimed to investigate the existence of associations between well-established and newly recognized biological and phenotypic features of breast cancer involved in tumor progression and prognosis. <i>Methods:</i> Ninety-eight cases of invasive breast cancer were assessed for the immunohistochemical expression of estrogen and progesterone receptors, Ki-67, HER2, Akt-1, and Notch-2, using the tissue microarray technique. Data regarding tumor histotype, histological grade, tumor size and lymph node status were collected for each patient and included in the analysis. <i>Results:</i> Several significant associations between histological and/o…

Analysis of tissue and circulating microRNA expression during metaplastic transformation of the esophagus

Genetic changes involved in the metaplastic progression from squamous esophageal mucosa toward Barrett's metaplasia and adenocarcinoma are almost unknown. Several evidences suggest that some miRNAs are differentially expressed in Barrett's esophagus (BE) and esophageal adenocarcinoma. Among these, miR-143, miR-145, miR-194, miR-203, miR-205, miR-215 appear to have a key role in metaplasia and neoplastic progression. The aim of this study was to analyze deregulated miRNAs in serum and esophageal mucosal tissue biopsies to identify new biomarkers that could be associated with different stages of esophageal disease. Esophageal mucosal tissue biopsies and blood samples were collected and analyz…

Class IIa HDACs repressive activities on MEF2-depedent transcription are associated with poor prognosis of ER⁺ breast tumors.

MEF2s transcription factors and class IIa HDACs compose a fundamental axis for several differentiation pathways. Functional relationships between this axis and cancer are largely unexplored. We have found that class IIa HDACs are heterogeneously expressed and display redundant activities in breast cancer cells. Applying gene set enrichment analysis to compare the expression profile of a list of putative MEF2 target genes, we have discovered a correlation between the down-regulation of the MEF2 signature and the aggressiveness of ER(+) breast tumors. Kaplan-Meier analysis in ER(+) breast tumors evidenced an association between increased class IIa HDACs expression and reduced survival. The im…

High liver RBP4 protein content is associated with histological features in patients with genotype 1 chronic hepatitis C and with nonalcoholic steatohepatitis.

Abstract Background and aim To investigate the hepatic expression of retinol-binding protein-4 (RBP4) in chronic hepatitis C (CHC) and nonalcoholic steatohepatitis (NASH) patients, and its association with biochemical and histological patterns of liver damage. Materials and methods Sixty-six genotype 1 CHC and 32 NASH patients were tested for hepatic RBP4 expression. Liver expression at immunostaining was scored as 0 (slight), 1 (mild), 2 (moderate), and 3 (intense). In addition, the mRNA and the quantitative protein expressions of RBP4 were tested by PCR and by western blot, respectively, in 12 NASH and 28 CHC patients. Twelve subjects undergoing elective cholecystectomy served as controls…

C1q Production by Bone Marrow Stromal Cells

Rsponse to antiviral therapy and hepatic expression of cycloossogenases in chronic hepatitis C.

Immunophenotypic profile and role of adhesion molecules in splenic marginal zone lymphoma with bone marrow involvement

Abstract Splenic Marginal Zone Lymphoma (SMZL), with or without villous lymphocytes (VL+/-), is a low-grade lymphoproliferative disorder with constant involvement of the bone marrow (BM). Different BM infiltration patterns, mainly intra-sinusoidal, interstitial and nodular, have been described. Adhesion molecules (AMs) constitute a heterogeneous group of antigenic receptors playing a major role in leukocyte recruitment, in lymphocyte homing and in cellular-mediated immune response. Evolution and pattern of the BM infiltrate could be influenced by a variable expression of AM on SMZL lymphocytes. The degree and pattern of BM infiltration and the immunohistochemical expression of AM (H-CAM, BL…

Hepatic expression of cycloxygenase-2 in non-alcoholic fatty liver disease

Pleural epithelioid angiosarcoma with lymphatic differentiation arisen after radiometabolic therapy for thyroid carcinoma: immunohistochemical findings and review of the literature

Abstract Background Pleural angiosarcoma is a rare tumor that causes diffuse pleural thickening and effusion, mimicking mesothelioma. Immunohistochemistry is needed to highlight endothelial differentiation. We describe the first case of pleural angiosarcoma with lymphatic differentiation following radiometabolic therapy for thyroid carcinoma. Case presentation A 50-year-old man showed diffuse pleural thickening and effusion. Nine years earlier, he underwent thyroidectomy and radiometabolic therapy for thyroid carcinoma with lymph node metastases. Histologically, the tumor consisted of a solid proliferation of atypical epithelioid cells and anastomosed vascular spaces, lacking of red blood c…

Constant detection of cyclooxygenase 2 in terminal stages of myeloid maturation.

Immunophenotypic profile and role of adhesion molecules in splenic marginal zone lymphoma with bone marrow involvement

Il bright liver echopattern come strumento diagnostico non invasivo di steatosi nell'ipertransaminasemia criptogenetica

Identification of CD162 in plasma-cell dyscrasia.

Response to antiviral therapy and hepatic expression of cyclooxygenases in chronic hepatitis C

OBJECTIVES: The aims of this study were to investigate the expression of cyclooxygenase-1 and cyclooxygenase-2 (COX-1 and COX-2) in chronic hepatitis C (CHC) by immunohistochemistry, based on the hypothesis that COXs expression could vary according to genotype, viral load, liver steatosis, BMI and response to therapy and to determine whether the addition of selective COX inhibitors could have a rationale in increasing the efficacy of antiviral therapy. METHODS: We used 35 formalin-fixed, paraffin-embedded liver tissue samples obtained by needle biopsy from patients with CHC (17F/18M) with one of two types of genotype (1b and 3a). The presence of COX-1 and COX-2 in the cytoplasm of hepatocyt…

P-Selectin Glycoprotein Ligand-1 as a Potential Target for Humoral Immunotherapy of Multiple Myeloma (Supplementry Material)

Monoclonal antibodies (mAbs), successfully adopted in the treatment of several haematological malignancies, have proved almost ineffective in multiple myeloma (MM), because of the lack of an appropriate antigen for targeting and killing MM cells. Here, we demonstrate that PSGL1, the major ligand of P-Selectin, a marker of plasmacytic differentiation expressed at high levels on normal and neoplastic plasma cells, may represent a novel target for mAb-mediated MM immunotherapy. The primary effectors of mAb-induced cell-death, complement-mediated lysis (CDC) and antibody-dependent cellmediated cytotoxicity (ADCC), were investigated using U266B1 and LP1 cell-lines as models. Along with immunolog…

CD1A-positive cells and HSP60 (HSPD1) levels in keratoacanthoma and squamous cell carcinoma.

CD1a is involved in presentation to the immune system of lipid antigen derived from tumor cells with subsequent T cell activation. Hsp60 is a molecular chaperone implicated in carcinogenesis by, for instance, modulating the immune reaction against the tumor. We have previously postulated a synergism between CD1a and Hsp60 as a key factor in the activation of an effective antitumor immune response in squamous epithelia. Keratoacantomas (KAs) are benign tumors that however can transform into squamous cell carcinomas (SCCs), but the reasons for this malignization are unknown. In a previous study, we found that CD1a-positive cells are significantly more numerous in KA than in SCC. In this study…

Glypican-3 and Hep Par-1 are Useful Biomarkers in the Cytologic Assessment of Ascites.

Till date, the utility of cytologic assessment of ascites for the identification of hepatocellular carcinoma (HCC) cells is still debated and the usefulness of immunocytochemistry for glypican-3 (GPC3) and Hep Par-1 in this setting has not been reported. Liquid-based cytology of ascitic fluid of 28 cirrhotic patients was performed and the spots obtained were stained with hematoxylin and eosin, papanicolau, and with GPC3 and Hep Par-1 antibodies. GPC3 and Hep Par-1 antibodies stained positively the atypical cells in the ascites of 2 patients with HCC showing an exophytic growth pattern. The specimens of the patients with nonexophytic HCC, other non-HCC cancers, or cirrhosis stained negativel…

Mast cells contribute to autoimmune diabetes by releasing interleukin-6 and failing to acquire a tolerogenic IL-10+ phenotype

Mast cells (MCs) are innate immune cells that exert positive and negative immune modulatory functions capable to enhance or limit the intensity and/or duration of adaptive immune responses. Although MCs are crucial to regulate T cell immunity, their action in the pathogenesis of autoimmune diseases is still debated. Here we demonstrate that MCs play a crucial role in T1D pathogenesis so that their selective depletion in conditional MC knockout NOD mice protects them from the disease. MCs of diabetic NOD mice are overly inflammatory and secrete large amounts of IL-6 that favors differentiation of IL-17-secreting T cells at the site of autoimmunity. Moreover, while MCs of control mice acquire…

CD146+ bone marrow osteoprogenitors increase in the advanced stages of primary myelofibrosis

Abstract CD146+ bone marrow stromal cells have been recently recognized as clonogenic osteoprogenitors able to organize a complete hematopoietic microenvironment. In this study we used immunohistochemical analysis to investigate the contribution of CD146+ bone marrow osteoprogenitors to the stromal remodeling occurring in the different stages of primary myelofibrosis. We found that CD146+ cells sited at the abluminal side of the bone marrow vessels and branching among hematopoietic cells significantly increased in the advanced stages of primary myelofibrosis (p<0.001), paralleling the extent of fibrosis (r=0.916, p<0.0001) and the microvascular density (r=0.883, p<0.0001). Coherently with a…

Response to antiviral therapy and hepatic expression of cycloxigenases in chronic hepatitis C

Risposta alla terapia antivirale ed espressione epatica della ciclossigenasi nell’epatite C

Comparison of Histochemical Stainings in Evaluation of Liver Fibrosis and Correlation with Transient Elastography in Chronic Hepatitis.

Background and Aim. The best staining to evaluate liver fibrosis in liver hepatitis is still a debated topic. This study aimed to compare Masson’s trichrome (MT), Sirius Red (SR), and orcein stainings in evaluating liver fibrosis in chronic HCV hepatitis (CHC) with semiquantitative and quantitative methods (Collagen Proportionate Area (CPA) by Digital Image Analysis (DIA)) and correlate them with transient elastography (TE).Methods. Liver stiffness evaluation of 111 consecutive patients with CHC was performed by TE. Semiquantitative staging by Metavir score system and CPA by DIA were assessed on liver biopsy stained with MT, SR, and orcein.Results. MT, SR, and orcein staining showed concord…

Comparison of Histochemical Staining Methods and Correlation with Transient Elastography in Acute Hepatitis.

&lt;b&gt;&lt;i&gt;Objective:&lt;/i&gt;&lt;/b&gt; To compare Masson's trichrome (MT), Sirius red (SR) and orcein staining in acute hepatitis (AH) and to correlate them with&lt;b&gt; &lt;/b&gt;transient elastography (TE),&lt;b&gt; &lt;/b&gt;a noninvasive method to assess hepatic fibrosis. &lt;b&gt;&lt;i&gt;Methods:&lt;/i&gt;&lt;/b&gt; We evaluated liver stiffness by TE in a cohort of 34 consecutive patients and assessed MT-, SR- and orcein-stained biopsies using the METAVIR scoring system and digital image analysis (DIA). &lt;b&gt;&lt;i&gt;Results:&lt;/i&gt;&lt;/b&gt; MT and SR both showed severe fibrosis (stage III-IV, DIA = 12.7%). Orcein showed absent or mild fibrosis (stage 0-II, DIA = 4.…

Human bone marrow mesenchymal stem cells display anti-cancer activity in SCID mice bearing disseminated non-Hodgkin's lymphoma xenografts.

Background Although multimodality treatment can induce high rate of remission in many subtypes of non-Hodgkin's lymphoma (NHL), significant proportions of patients relapse with incurable disease. The effect of human bone marrow (BM) mesenchymal stem cells (MSC) on tumor cell growth is controversial, and no specific information is available on the effect of BM-MSC on NHL. Methodology/Principal Findings The effect of BM-MSC was analyzed in two in vivo models of disseminated non-Hodgkin's lymphomas with an indolent (EBV− Burkitt-type BJAB, median survival = 46 days) and an aggressive (EBV+ B lymphoblastoid SKW6.4, median survival = 27 days) behavior in nude-SCID mice. Intra-peritoneal (i.p.) i…

LncRNA H19, HOTAIR and MALAT1 as prognostic molecular biomarkers in GIST

Nodular histiocytic/mesothelial hyperplasia as consequence of chronic mesothelium irritation by sub-phrenic abscess.

Nodular histiocytic/mesothelial hyperplasia (NHMH) is a benign localized alteration, first described in 1975 by Rosai in the hernia sac [1]. Few pulmonary cases have been reported in literature [2–6]. Sometimes it has been reported in the pericardium [7,8] or presenting as an inguinal mass [9]. The ‘mesothelial/monocytic incidental cardiac excrescence’, first described by Weinot et al. in 1994 [10] is now considered a similar lesion to NHMH [11]. It consists of a reactive proliferation of histiocytes and mesothelium secondary to chronic irritation and it has been observed in pleura-damaging processes, such as pneumothorax [5], or as consequence of cardiac catheterization, inflammation, mech…

Cyclooxygenase-2 expression in chronic liver disease and hepatocellular carcinoma: an immunohistochemical study

UNLABELLED Hepatocarcinogenesis is a multistep process characterized by hepatocyte inflammation, regeneration, and proliferation. These changes are believed to depend on the aberrant expression of various tumor suppressor genes, oncogenes and growth factors. Several studies have shown the involvement of cyclooxygenase-2 (COX-2), the inducible isoform of the enzymes that catalyze prostaglandin synthesis in various aspects of carcinogenesis. COX-2 has been described as being overexpressed in hepatocellular carcinoma (HCC) patients. Using immunohistochemistry, we studied COX-2 expression in different chronic liver diseases (CLD) including nonalcoholic steatohepatitis (NASH), chronic hepatitis …

Exploratory study on the effects of biodegradable nanoparticles with drugs on malignant B cells and on a human/mouse model of Burkitt lymphoma.

The aim of this study was to determine if Rituximab coated Biodegradable Nanoparticles (BNPs) loaded with Chlorambucil and Hydroxychloroquine could induce apoptosis of B-Chronic Lymphocytic Leukemia (B-CLL), MEC-1 and BJAB cells in vitro and evaluate their toxic and therapeutic effects on a Human/Mouse Model of Burkitt Lymphoma at an exploratory, proof of concept scale. We found that Rituximab-Chlorambucil-Hydroxychloroquine BNPs induce a decrease in cell viability of malignant B cells in a dose-dependent manner. The mediated cytotoxicity resulted from apoptosis, and was confirmed by monitoring the B-CLL cells after Annexin V/propidium iodide staining. Additional data revealed that these BN…

Different immunophenotypical apoptotic profiles characterise megakaryocytes of essential thrombocythaemia and primary myelofibrosis.

Aims: Essential thrombocythaemia (ET) and primary myelofibrosis (PMF) share some clinical and pathological features, but show different biological behaviour and prognosis. The latest contributions to understanding the nature of these disorders have focused on bone marrow microenvironment remodelling and proliferative stress, recognising megakaryocytes (MKCs) as “key-cells”. The aim of this study was to investigate the apoptotic profile of ET and PMF MKCs in order to further characterise the biology of these disorders. Methods: Bone marrow biopsy samples from 30 patients with ET, and 30 patients with PMF, were immunophenotypically studied for the expression of pro-apoptotic (Fas, Fas-L, Bax,…